Cytoplasmic free ionic calcium above a critical concentration is required for contraction of vascular smooth muscle fibers. It is postulated that sodium entry down its electrochemical grandient supplies the necessary energy to drive calcium out of the fiber via a counter-exchange carrier system. Since homeostatic mechanisms tend to maintain extracellular sodium concentration relatively constant, the transmembrane sodium electrochemical gradient (and with it the degree of vascular smooth muscle contraction) is primarily controlled by the active sodium pump. Therefore, any manipulation of sodium pump activity should be reflected in alterations of vascular tone. Pump activity alteration is possible by using cardiac glycosides, altering extracellular sodium or potassium and indirectly by ionic channel blockers. There is a possiblity that naturally occurring Na -K ions dependent ATPase inhibitors exist, e.g. natriuretic hormone, which presumably acts by inhibition of sodium pumps in renal tubules. Such material may have ubiquitous pump inhibitory properties. If so they may be importantly involved in the etiology of essential hypertension. The objectives of the proposed studies are to correlate vascular resistance to blood flow with putative alterations in sodium pumping and to examine the effect, if any, of natriuretic factors in alterations in vascular tone. The experiments will be performed on isolated hindlimb perfusion preparations in which all hormonal and neural influences on the vasculature will be have been withdrawn. Ionic concentrations of perfusates will be altered while recording arterial perfusion pressure using a constant flow regimen. Drug administration can be achieved in the same manner. Natriuretic factor, will be obtained from extracellular fluid-expanded, urine-reinfused animals.